Services

MRIF offers in vivo MRI-based molecular and cellular imaging services, including:

Consultation Services:

UPCI animal researchers first meet with Dr. Wiener to discuss their research objectives and long term goals, to better identify the magnetic resonance imaging & spectroscopy (MRI&S) methods that best fit their needs. Dr. Wiener then brings these needs to the attention of a joint MRI and PET internal advisory committee, and the group discusses the appropriate modality or modalities. The appropriate MRI core faculty member then meets with the UPCI investigators and Dr. Wiener to discuss the specifics of the tumor models and the implementation of the particular MRI methods that meet those objectives. Dr. Boada performs a similar role with clinical faculty members of the UPCI. Most UPCI investigators lack exposure to and experience with MRI; these consultative sessions provide researchers with important awareness of the full capabilities of MRI.

MR Imaging:

Compared to survival studies, MRI gives UPCI investigators both earlier end points for assessing the efficacy of new treatments, and also insight into the molecular reasons why these new treatments may or may not work. The information provides specificity with respect to the treatments effect on the tumor, and can even be used to identify the onset of tumor resistance to a given therapy. The methodologies offered by the Facility include:

  • Tumor volume measurements, which are simple measurements that directly assess the effect of a new treatment on a particular tumor type. Unlike survival studies, tumor volume studies allow an investigator to observe partial effects, and even temporary remission, with the implicit subsequent development of tumor resistance.
  • Measurements of tumor capillary transfer rates or permeability surface area products, tumor vascular plasma fraction, and extracellular volume space, which can give physiological information about a treatment protocol at earlier stages than even tumor volume measurements. For example, these measurements provide insights into the molecular mechanisms and the efficacy of anti-VEGF and antiangiogenesis treatments. They also enable in vivo analyses of drugs targeted to disrupt specific signaling cascades in endothelial cells, and whether they affect the end points of these signaling cascades. In the case of brain tumors, these types of measurements are one of the few that can differentiate between radiation-induced scarring and recurrent or residual tumor.
  • Measurement of tumor metabolites and drug concentrations with MRI&S enables the in vivo monitoring of drug pharmacokinetics, drug activation, and tumor biology. It provides vital information on the actual conversion of prodrugs into active drugs or drugs into inactive metabolites, and the intratumoral concentration of these drugs. These methods also allow investigators to monitor changes in tumor biochemistry as a function of treatment, growth, or metastatic potential.
  • The synthesis of targeted and macromolecular MR contrast agents. The use of macromolecular contrast agents provides better methods for monitoring tumors in organs other than the brain, when combined with measurements of tumor capillary physiology and function. The existence of the blood brain barrier in healthy brain tissue creates a zero baseline value for tumor capillary transfer rates and tumor extracellular extravascular space measured with water soluble MRI contrast agents. Brain tumor capillaries have a significant increase in these parameters from zero. In other organs, the tumor capillary transfer rates and tumor extracellular extravascular space have values well above zero for standard MRI contrast agents, and this obscures small changes associated with tumor capillaries and their responses to therapy in these organs. Macromolecular agents have tumor capillary transfer rates or permeability surface area products that vary with the size and charge of the agent, and the relative changes above background are larger, making them a better choice for tumors outside of the brain. Tumor-specific agents provide an additional means of directly monitoring tumor response, differentiating tumor types, confirming secondary tumors, and a method for differentiating tumors from scar tissue.
  • Applications and development of techniques based on single and multiple quantum methods, for the measurement of low sensitivity nuclei, low concentration metabolites, and for directly detecting low concentrations of drugs. These methods provide a means of studying tumor biochemistry, drug activation, intra-tumoral drug concentrations, and intratumoral drug pharmacokinetics.
  • Monitoring and measuring cell movements into and recruitment by tumors in vivo. Lymphocyte, adoptively transferred immune cell, and stem cell tracking provides a means of monitoring different types of immunotherapy, how the tumor environment affects immune cells, if a treatment protocol even results in attracting immune cells to the tumor, and if stem cells home in on specific targets.
  • Custom methods development. Services are developed through user input and surveying the UPCI community as needed. Examples include regional blood volume measurements and perfusion studies. All of these methods provide UPCI investigators with tools that generate more information, and also have the potential to greatly benefit cancer research, clinical trials, and cancer treatments. The UPCI has a large number of investigations that involve biological therapeutics, anti-angiogenesis therapies, drug pharmacokinetic studies, MR spectroscopy of breast cancer, and earlier biochemical markers of the transformed phenotype. These methods will lead to quicker noninvasive methods for diagnosing and staging primary or metastatic tumors, and better monitoring of tumor responses to therapeutic protocols or standard treatments.